The neural correlates of cognitive control have been studied extensively using various neuroimaging techniques. Certain theoretical accounts posit a major role of the anterior cingulate cortex (ACC) in networks hypothesized to underlie conflict monitoring and resolution. However, the scope of these accounts has proven limited. We argue that conflict is only a special case of uncertainty that can be quantified as information entropy, based on an information theory framework. In conjunction with the existence of a robust relationship between functional activation of regions in a frontoparietocingulate system and reaction time performance across various behavioral tasks requiring cognitive control, as well as observation of a special class of neurons found in the ACC that are well suited for rapid and long distance integration of information among distributed regions involved in cognitive control, we propose a frontoparietocingulate system model of cognitive control in which the ACC plays a major role in signaling uncertainty. In order to test this model, we have designed a series of experiments with various information theoretic measures and propose to examine functional activity and connectivity of the frontoparietocingulate system as a function of information entropy using functional magnetic resonance imaging. This study not only challenges the current theories of cognitive control, but also has a wide ranging impact within the field of cognitive neuroscience as well as studies on the disruption of cognitive control in a variety of major psychiatric disorders. PUBLIC HEALTH RELEVANCE: Deficits in cognitive control of information processing may be present in many forms of psychopathologies, such as schizophrenia and autism, for which current data suggest aberrant selection of information for conscious processing. In order to advance the study of these and other disorders, however, it is important to focus on the interplay of structures composing the networks that underlie these functions in healthy adults. The aim of the current proposal is to characterize these networks and their interactions with specific emphasis on the frontoparietocingulate system in a population of healthy adult volunteers, so as to advance the theory related to the cognitive control of information processing, and to facilitate translational research via development of comprehensive and wide-reaching models of the neurobiological underpinnings of cognitive control of information processing.